The objective of the proposed studies is to analyze the ability of microorganisms from the periodontal pockets of humans with different forms of periodontal disease to degrade human IgA, IgG and IgM into Fc and Fab fragments and to investigate the ability of these immunoglobulin fragments to induce humoral and cellular responses. The recent demonstration that several strains of Bacteroides and Capnocytophaga, can degrade human IgA and IgG and that closely related, yet apparently non-pathogenic bacteria lack this property implicates immunoglobulin protease activity as an important virulence factor in the pathogenesis of oral disease. In this regards, Fc fragments can induce murine splenic B cells and human peripheral blood lymphocytes to proliferate and differentiate into antibody secreting cells. Therefore, an in vitro examination of immunoglobulin protease activity generated by microbial isolates sampled from subgingival pockets of patients with localized and generalized forms of juvenile periodontites, insulin-dependent diabetes mellitus, and adult onset periodontitis will be performed. Gingival crevicular fluid will be obtained from these same patients and analyzed for the presence of Fc/Fab fragments in order to correlate their presence with active proteolysis and destructive periodontal disease. Patients' peripheral blood lymphocytes will be isolated and stimulated in vitro with Fc/Fab fragments generated by proteases derived from isolated plaque organisms. The humoral and cellular aspects of the response will be evaluated.